Biopsy localization method and device

ABSTRACT

A biopsy localization device made according to the invention includes a bioresorbable element, such as a cellulose. The bioresorbable element preferably carries a radiopaque marker. The bioresorbable element preferably swells to fill the biopsied open region. The bioresorbable element and radiopaque marker permit the biopsy site to be relocated by various techniques, including mammography and ultrasound. In addition, the bioresorbable element can be used as a therapeutic tool for treatment of the diseased lesion and for hemostasis.

This application is a continuation of U.S. application Ser. No.10/027,157, filed Dec. 20, 2001, now issued as U.S. Pat. No. 6,730,042,which is a continuation of U.S. application Ser. No. 09/900,801, filedJul. 6, 2001, now issued as U.S. Pat. No. 6,699,205, which is acontinuation of U.S. application Ser. No. 09/336,360, filed Jun. 18,1999, now issued as U.S. Pat. No. 6,270,464, which application claimsthe benefit of the following provisional patent applications: BiopsyLocalization Device, Application No. 60/090,243, filed Jun. 22, 1998;Biopsy Localization and Hemostasis Device, Application No. 60/092,734,filed Jul. 14, 1998; Device and Method of Biopsy Localization andHemostasis, Application No. 60/114,863, filed Jan. 6, 1999; and Deviceand Method of Biopsy Localization, Hemostasis & Cancer Therapy,Application No. 60/117,421, filed Jan. 27, 1999.

BACKGROUND OF THE INVENTION

In the U.S. alone approximately one million women will have breastbiopsies because of irregular mammograms and palpable abnormalities. SeeFIG. 1 which diagrams the current treatment algorithm for non-palpablebreast lesions. Biopsies can be done in a number of different ways fornon-palpable lesions, including surgical excisional biopsies andstereotactic and ultrasound guided needle breast biopsies. In the caseof image directed biopsy, the radiologist or other physician takes asmall sample of the irregular tissue for laboratory analysis. If thebiopsy proves to be malignant, additional surgery (typically alumpectomy or a mastectomy) is required. The patient then returns to theradiologist a day or two later where the biopsy site (the site of thelesion) is relocated by method called needle localization, apreoperative localization in preparation for the surgery.

Locating the previously biopsied area after surgical excision type ofbiopsy is usually not a problem because of the deformity caused by thesurgery. However, if the biopsy had been done with an image directedneedle technique, as is common, help in relocating the biopsy site isusually needed. One procedure to permit the biopsy site to be relocatedby the radiologist during preoperative localization is to leave some ofthe suspicious calcifications; this has its drawbacks.

Another way to help the radiologist relocate the biopsy site involvesthe use of a small metallic surgical clip, such as those made byBiopsys. The metallic clip can be deployed through the biopsy needle,and is left at the biopsy site at the time of the original biopsy. Withthe metallic clip as a guide, the radiologist typically inserts a barbedor hooked wire, such as the Hawkins, Kopans, Homer, Sadowski, and otherneedles, back into the patient's breast and positions the tip of thewire at the biopsy site using mammography to document the placement. Thepatient is then taken to the operating room with the needle apparatussticking out of the patient's breast. While the clip provides a goodindication of the biopsy site to the radiologist during preoperativelocalization, the clip remains permanently within the 80% of patientswith benign diagnoses. Also, because the clip is necessarily attached toa single position at the periphery of the biopsy site, rather than thecenter of the biopsy site, its location may provide a misleadingindication of the location of diseased tissue during any subsequentmedical intervention. In addition, the soft nature of breast tissuepermits the tip of the barbed or hooked needle to be relatively easilydislodged from the biopsy site. The clip is also relatively expensive.

Another localization method involves the use of laser light from the tipof a optical fiber connected to a laser. A pair of hooks at the tip ofthe optical fiber secures the tip at the biopsy site; the glow indicatesthe position of the tip through several centimeters of breast tissue.This procedure suffers from some of the same problems associated withthe use of barbed or hooked wires. Another preoperative localizationprocedure injects medical-grade powdered carbon suspension from thelesion to the skin surface. This procedure also has certain problems,including the creation of discontinuities along the carbon trail.

SUMMARY OF THE INVENTION

The present invention is directed to a biopsy localization method anddevice which uses a locatable bioabsorbable element left at the biopsysite so that if testing of the biopsy sample indicates a need to do so,the biopsy site can be relocated by finding the bioabsorbable element.This eliminates the need to use of metallic clips during biopsies andoften eliminates the need for a return to the radiologist forpreoperative needle localization. In addition, the bioabsorbable elementcan be used as a therapeutic tool for treatment of the diseased lesionand for hemostasis.

A biopsy localization device made according to the invention includes abioabsorbable element delivered in a pre-delivery state to a soft tissuebiopsy site of a patient by an element delivery device. Thebioabsorbable element may be palpably harder than the surrounding softtissue at the biopsy site when in the post-delivery state.

One preferred material used as the bioabsorbable element is a dehydratedcollagen plug. This type of plug may swell and is palpable forsubsequent location by the surgeon. The collagen plug may not swell atall. In some situations, such as with small breasted women or where thebiopsy site is close to the surface, a non-swellable bioabsorbablematerial, such as a round pellet of PGA, can be used instead of aswellable bioabsorbable material. The bioabsorbable material can also bemade so that it is absorbed quickly to produce a local tissueinflammation; such a localized inflammation can be used to locate thebiopsy site instead of location by palpation. Instead of leaving, forexample, a collagen plug, a PGA pellet or a bioabsorbable suturematerial at the biopsy site for location by palpation or inflammation, alength of bioabsorbable suture material, a collagen filament, or otherbioabsorbable material extending from the biopsy site out through theskin can be used. In this case the surgeon can follow the bioabsorbablesuture material to the biopsy site in a manner similar to that used withHawkins needles. In other cases, such as in the case of a deeply locatedlesion or large breast, the bioabsorbable material may need to belocated by the radiologist, by for example, ultrasound or mammography.In any event the bioabsorbable material will typically be absorbedwithin about a month of placement. The invention thus eliminates the useof metal clips during biopsies and usually eliminates the need forreturn to the radiologist for preoperative localization.

While the primary use of the device is intended to localize the site ofneedle biopsies for possible future surgical excision, the device mayalso be useful in marking the site of surgical excisional biopsies. Forexample, during a wide surgical excision for cancer diagnosed by arecent surgical excisional biopsy, surgeons frequently have difficultyin determining the precise relationship of the previously excised tissueto the surgical wound. Therefore, more tissue is removed than might havebeen removed had the exact location of the previous lesion been moredefinite. With the present invention, a bioabsorbable element may beinserted into the biopsy site during a surgical excisional biopsy beforethe wound is closed to mark the site for potential wide excision shouldthe biopsy reveal cancer. Alternatively, a bioabsorbable element may beplaced at the biopsy site using a delivery device by partially orcompletely closing the wound and then depositing the bioabsorbableelement through the delivery device and removing the delivery devicethrough the closed incision. The presence of the palpable marker withinthe previous excisional biopsy site would allow the surgeon to moreeasily and confidently remove tissue around this site, and preserve morenormal breast tissue.

Another use of the device is to primarily localize a non-palpable lesionprior to surgical excisional biopsy. Instead of using the needle/wireapparatus which has a tendency to migrate and become dislodged withtraction, the palpable marker may be inserted into the suspicious areaof the breast under mammographic or ultrasonic guidance immediatelyprior to the surgical excisional biopsy. This would provide a palpablelocator for the surgeon as described above. In this instance, the markerwould only need to be palpable, and not necessarily bioresorbable, sincethe intent would be to remove it in all cases.

In addition to permitting the biopsy site to be located by subsequentpalpation or other means, the invention also can provide hemostasis andtherapeutic benefits. The bioabsorbable element may comprise atherapeutic agent; the therapeutic agent may comprise at least a chosenone of a chemotherapeutic agent, a radiation agent and a gene therapyagent. Since the bloabsorbability can be varied from a day or two to ayear or more, the material may be used to treat the diseased tissue andnot just locate it. Some current therapies include radiation,chemotherapy, gene therapy as well as other technologies and therapies.Because the bioabsorbability can be easily varied, a medium can be placeinto the bioabsorbable element and be externally excited or triggered inthose cases where the biopsy results are malignant. Further, thebioabsorbability concept can be used for future implantation of atherapeutic agent. For example, if the bioabsorbable element is adehydrated collagen, this material could be used as a reservoir for, forexample, delivery of materials that effect chemotherapy, brachytherapy,etc. Once the laboratory results are received and show the biopsy ismalignant and therapy is required, by surgical excision or otherwise,the physician may inject, for example, a radiation pellet, achemotherapeutic agent or a gene therapeutic agent into or adjacent tothe bioabsorbable element for direct treatment of the diseased tissue.

The change in the bioabsorbable element can be via one of several ways,such as hydration or desiccation, change in temperature, electricalstimulation, magnetic stimulation, chemical or physical reaction withanother material, additives, enzymatic reactions, ionization, electricalcharges, absorption, as well as other means. The invention may employone or more of these techniques or measures or others, to change theconsistency, hardness and or size of the bioabsorbable element betweenits deployed and non-deployed states. The visual detectability of thebioabsorbable element may be aided by the use of a coloring agent, suchas methylene blue or some other dye. The radiographic detectability ofthe element may be enhanced by a radiopaque marker. As well, ultrasonicdetectability may be enhance by special treatment of the bioresorbableelement.

The bioresorbable element may have margins which are roughened so as toprevent migration within the tissues. Filaments extending from themargins of the bioresorbable element may be utilized also to stabilizethe position of the device within the cavity. The filaments may or maynot be composed of the same material as the bioresorbable element.

The provision of hemostasis helps to lessen the bleeding and swellingwithin and about the biopsy site. This can be accomplished by physicalor chemical means. That is, the device may swell so that it essentialfills the biopsy cavity or the device may have a chemical reaction withblood or blood products to cause effective blood clotting, or both.Other methods for causing local hemostasis are also possible with theinvention.

Other features and advantages of the invention will appear from thefollowing description in which the preferred embodiments and methodshave been set forth in detail in conjunction with the accompanydrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow diagram of a conventional treatment algorithm fornonpalpable breast lesions;

FIG. 2 is a flow diagram of a treatment algorithm according to thepresent invention;

FIG. 3 is a simplified view illustrating a biopsy needle assemblyobtaining a tissue sample of an abnormality at a target site;

FIG. 4 illustrates the main housing and sheath of the needle biopsyassembly left in place after the tissue sample has been removed leavinga biopsied open region at the target site;

FIG. 5 illustrates the barrel of the delivery device of FIG. 4 insertedinto the main housing of the biopsy needle assembly and the plungerdepressed injecting the bioabsorbable element into the biopsied openregion, thus effectively filling the biopsied open region at the targetsite;

FIG. 6 illustrates the location of the bioabsorbable element of FIG. 5with the surgeon using his or her fingers; and

FIG. 7 illustrates a bioabsorbable thread extending from thebioabsorbable element of FIG. 5 up through the patient's skin, thethread being delivered to the bioabsorbable element using the deliverydevice of FIGS. 4 and 5.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

FIG. 2 illustrates a treatment algorithm 2 according to the presentinvention. As a result of a routine mammography 4, a tumor or otherabnormality may be detected as at 6. The typical response will ofteninclude additional magnification mammograms or a follow-up mammogramscheduled for some time in the future, such as six months. This isindicated at 8. If the tumor is not palpable, see 9, an image guidedneedle biopsy by a breast radiologist is typically conducted as at 10.Image guided needle biopsies can be done in a number of ways. Presently,stereotactic (x-ray) and ultrasound guided needle biopsies are commonlyused, primarily because of their accuracy, speed and minimal trauma tothe patient. Stereotactic needle biopsies typically use a stereotactictable, such as made by Fisher or Lorad, which provides mammography(x-ray) guidance to a biopsy needle assembly. Ultrasound guided biopsiescan be conducted with any one of a number of commercially availableinstruments. An exemplary biopsy needle assembly 14, illustrated in FIG.3, includes a biopsy needle 13 passing through a sheath 20 extendingfrom a hollow main housing 22. The tip 12 of biopsy needle 13 of biopsyneedle assembly 14 is automatically inserted to the abnormality 16 atthe target site 18. Biopsy needle 13 has a laterally directed sideopening 24 adjacent to tip 12 used to capture a tissue sample ofabnormality 16. Once the tissue samples have been obtained, the removedtissue creates a biopsied open region 26 at target site 18. See FIG. 4.Following the removal of biopsy needle 13 from sheath 20 and mainhousing 22, the barrel 30 of a bioabsorbable element delivery device 32is inserted through main housing 22 and into sheath 20. Barrel 30contains a bioabsorbable element 34, see FIG. 5 Bioabsorbable element 34is, in this preferred embodiment, a plug of dehydrated collagen, such asthat sold by several companies such as Davol, Datascope, Integra LifeSciences, Collagen Matrix, Vascular Solutions, et al. Bioabsorbableelement 34 may swell on contact with an aqueous liquid within biopsiedopen region 26 and substantially fills the biopsied open region assuggested in FIG. 5. In this preferred embodiment, bioabsorbable element34 is transformed from its pre-delivery state within barrel 30 to itspost-delivery state at region 26 and in the process swells and becomessomewhat softer in its post-delivery state than in its pre-deliverystate. However, in its post-delivery state, bioabsorbable element 34 ispalpably harder, preferably at least about 1.5 times harder, than thesurrounding soft tissue, typically breast tissue 36. This permitsbioabsorbable element 34 at the target site 18 to be relocated bypalpation of the patient by the physician, see FIG. 6, to find thebioabsorbable element 6 and as discussed in more detail below.

A bioabsorbable element could be made of materials other than collagenand could be in a form other than a solid, relatively hard plug in itspre-delivery state. For example, bioabsorbable element 34 in itspre-delivery state within barrel 30 could be in a liquid or otherwiseflowable form; after being deposited at open region 26 at target site18, the bioabsorbable element could change to become palpably harderthan the surrounding tissue 36 to permit subsequent relocation of targetsite 18 by palpation. In some situations, it may be desired thatbioabsorbable element 34 not change its size or hardness between itspre-delivery state and its post-delivery state, such as being palpablyharder than the surrounding tissue 36 in both states. In a preferredembodiment, transformation of bioabsorbable element 34 is by contactwith an aqueous liquid.

However, transformation of the bioabsorbable element, which can be interms of, for example, hardness, texture, shape, size, or a combinationthereof, can be due to other factors, such as application of thermalenergy, radiation, magnetic energy, etc.

Returning again to FIG. 2, it is seen that after insertion ofbioabsorbable element 34, the biopsy sample is sent to pathology forevaluation at 36. If the pathology report, which is available a day ortwo after the biopsy, is benign, the patient is so informed and thebioabsorbable element simply is absorbed by the patient within, forexample, a month as at 38. If the pathology report is positive, so thatcancer is found, the biopsied open region 26 at the target site 18 islocated by the surgeon by palpation as suggested by FIG. 6. Afterfinding the target site by palpation, which eliminates the need forpreoperative localization by the radiologist, appropriate medicaltreatment, such as excisional surgery, can be performed.

If the tumor is palpable, the surgeon may choose to make a directincisional biopsy as at 48. According to the present invention,bioabsorbable delivery device 32 could be used to place bioabsorbableelement 34 at the site of the incisional biopsy. After removal ofdelivery device 32, the incision would be closed, the biopsy samplewould be sent to pathology and the patient would go home with theprocedure preceding as discussed above, starting with item 36.

It may be preferred that bioabsorbable element 34 also act as ahemostatic agent to stop bleeding at site 18 by virtue of physicalmeans, by filling or substantially filling open region 26, as well aschemical means through the chemical interaction, such as coagulation,with blood components. In addition, bioabsorbable element 34 could becovered by a non-hemostatic degradable outer layer so that hemostasis orother action is delayed until the outer layer has been eroded. In somesituations, it may be necessary or at least desirable to shield thebioabsorbable element from the blood or other body fluids until afterthe bioabsorbable element is in place at target site 18. This could beaccomplished by, for example, physically isolating the bioabsorbableelement from body fluids by using a removable physical barrier duringdelivery of the bioabsorbable element. Alternatively, a bioabsorbablecoating or layer, as described above, may be used. The bioabsorbableelement may be changed from its pre-delivery state to its post-deliverystate in a variety of manners including hydration, changing thetemperature, electrical stimulation, magnetic stimulation, chemicalreaction with a stimulating agent, physically interaction with anactivating member (such as a knife blade which could be used to sliceopen a capsule containing the bioabsorbable element), by ionizing thebioabsorbable element, or by absorption or adsorption of a fluid by thebioabsorbable element.

The invention may also be used to medically treat the patient. That is,the bioabsorbable element-could include a therapeutic element whichwould be activated only if the pathology report indicated the need forthe medical treatment. Various ways of activating an agent in abioabsorbable element could be used, such as injecting aradiation-emitting element at the vicinity of the target site,externally irradiating the target site, providing a triggering substanceto the target site, manual pressure, photodynamic therapy, sclerosingchemistry, vibrational therapy, ultrasound, and the like. Alternatively,the bioabsorbable element could be made so that it includes no suchactivating agent; rather, medical treatment could be provided by, forexample, delivery of a chemotherapy agent, a radiation emitting element,thermal energy, electrical energy, vibrational energy, gene therapy,vector therapy, anti-angiogenesis therapy. To facilitate the delivery,the bioabsorbable element may contain a radiopaque marker or may haveproperties to aid in detecting it by ultrasound, in addition to beingpalpable.

An important use for the invention is in the treatment of breast cancer.In one embodiment, it is desirable that bioabsorbable element 34 in itspost-delivery state have a hardness of at least about one and a halftimes that of breast tissue so that it is palpably harder than thesurrounding tissue. Also, it is desired that bioabsorbable element 34,in one embodiment, swells from its pre-delivery state to itspost-delivery state so to fill or at least substantially fills openregion 26. To achieve this it is preferred that bioabsorbable element 34swells about 50 to 1500%, and more preferably about 100 to 300%, fromthe pre-delivery state to the post delivery state, typically when placedin contact with an aqueous liquid. It is preferred that thebioabsorbable element has a longest dimension of at least about 0.5 cmin its post-delivery state to aid its location by palpation.

While the bioabsorbable element is preferably made of collagen in oneembodiment, the bioabsorbable element can include, for example, one ormore of the following materials; polyactic and polyglycolic acids,polyorthoesters, resorbable silicones and urethanes, lipids,polysaccharides, starches, ceramics, polyamino acids, proteins,hydrogels and other gels, gelatins, polymers, cellulose, elastin, andthe like.

In some situations it may be desired to use a bioabsorbable filament 44extending from bioabsorbable element 34 through the patient's skin 46 asshown in FIG. 7. This can be accomplished by delivering bioabsorbablefilament 44 through sheath 20 as bioabsorbable element 34 is injectedinto region 26 at target site 18. In some situations it may not bepossible or desirable to use bioabsorbable element 34; in thosesituations it may be useful to provide for only bioabsorbable filament44 extending from target site 18 to above the patient's skin 46.

While it is presently preferred that bioabsorbable element deliverydevice 32 be guided through a portion of needle assembly 14, that issheath 20 and main housing 22, in some situations it may be useful tocover sheath 20 with an outer sheath which would be left in place afterthe biopsy sample has been removed and the entire biopsy needle assembly14 has been removed. The sheath left in place would then be used toguide barrel 30 of delivery device 32 to target site 18. Of course,delivery device 32 could take a number of different forms such as asyringe containing fluid or paste that is injected through a needle orthrough the housing 22 and sheath 20 or through an outer sheath.Alternatively, other delivery devices could be employed for delivery ofbioresorbable element 34.

The invention has applicability toward the correction of a defect thatis caused by breast tissue removal for biopsy or diseased tissueremoval. Collagen is often placed in the body where it is eventuallyreplaced by human autogenous tissue. Hence, the invention could be usedfor the repair of tissue that has been damaged due to tissue removal.The delivery device described heretofore could be used for installing amaterial (synthetic or mammalian) into the cavity for such a cosmetic orreconstructive repair. The material would typically be an effectivelynon-bioabsorable material, such as a silicon gel-filled capsule or bag.

Modification and variation can be made to the disclosed embodimentswithout departing from the subject of the invention as defined in thefollowing claims.

Any and all patents, patent applications, and printed publicationsreferred to above are incorporated by reference.

1. A method for marking a biopsy cavity comprising the steps of:providing a substantially dehydrated bioresorbable body having aradiopaque marker carried by the bioresorbable body, said bioresorbablebody comprising cellulose; removing a biopsy specimen from the breast ofa patient, thereby creating a biopsy site; inserting the bioresorbablebody into the biopsy site to mark the location of the biopsy site,wherein the bioresorbable body after insertion contacts body fluid andswells to substantially fill the biopsy site.
 2. The method of claim 1,further comprising the step of relocating the biopsy site by detectingthe radiopaque marker.
 3. The method of claim 1, wherein thebioresorbable body comprises a single bioresorbable body.
 4. The methodof claim 1, wherein the radiopaque marker is contained within thebioresorbable body.
 5. The method of claim 1, wherein the radiopaquemarker is detected by mammography.
 6. The method of claim 1, wherein theradiopaque marker is detected by ultrasound.
 7. The method of claim 1,wherein the bioresorbable body swells about 100 to 300 percent in a postdelivery state of the bioresorbable body relative to a pre-deliverystate of the bioresorbable body.
 8. The method of claim 1, wherein thebioresorbable body is softer in a post delivery state of thebioresorbable body than in a pre-delivery state of the bioresorbablebody.